Sickle Cell Disease (SCD) is an abnormality of red blood cells (RBC) that affects approximately 72,000 people in the United States, or approximately 1 in every 500 African-Americans. With current therapies, the mortality in the United States is 50 percent by age 40. SCD is a chronic, debilitating disease associated with frequent painful crises, acute chest syndrome, stroke, and renal failure. As a result, patients require frequent hospitalizations and experience absenteeism from work. The only cure for SCD to date is bone marrow transplantation (BMT). However, at present the morbidity and mortality associated with ablative BMT has limited the widespread application of this approach. Moreover, the requirement for a perfectly matched donor has limited BMT to only 17 percent of candidates. We have developed an approach to engineer a bone marrow graft to avoid the major complications of BMT: graft-versus-host reactivity (GVHD); graft failure; and the need for perfect matching. Our approach is superior to current therapies because it involves a proprietary process that enriches for patented facilitating cells (FC) and stem cells but removes GVHD-producing cells. In this proposal we will utilize this FCRx product, already demonstrated to be effective for treatment of leukemic patients, for treatment of patients with SCD. In phase I, we will develop a nonmyeloablative conditioning approach to establish 20 percent donor chimerism. The well defined end point will be engraftment and production of normal RBC. In the long term we will develop and market a quality controlled/quality assured FDA-approved bone marrow product (SCD FCRx) to treat individuals with SCD. Our platform technology will be provided to hospital systems worldwide as an FDA-approved bioservice. Such a treatment approach could be expanded to other blood disorders, including thalassemia. The complimentary structure and expertise of the company and the University lends itself nicely to this joint effort. The company will develop a strategy to produce and market the product while the University will conduct the clinical trial and process the marrow in its FACT-accredited cell processing facility.